L-alpha-glycerylphosphorylcholine reduces the microcirculatory dysfunction and nicotinamide adenine dinucleotide phosphate-oxidase type 4 induction after partial hepatic ischemia in rats

Background

We set out to investigate the microcirculatory consequences of hepatic ischemia–reperfusion (IR) injury and the effects of L-alpha-glycerylphosphorylcholine (GPC), a deacylated phospholipid derivative, on postischemic hepatocellular damage, with special emphasis on the expression of nicotinamide adenine dinucleotide phosphate oxidase type 4 (NOX4), which is predominantly expressed in hepatic microvessels.

Materials and methods

Anesthetized male Sprague–Dawley rats were subjected to 60-min ischemia of the left liver lobes and 180-min reperfusion, with or without GPC treatment (50 mg/kg intravenously 5 min before reperfusion, n = 6 each). A third group (n = 6) served as saline-treated control. Noninvasive online examination of the hepatic microcirculation was performed hourly by means of modified spectrometry. Plasma tumor necrosis factor (TNF-α), high-mobility group box 1 protein (HMGB1), plasma aspartate aminotransferase, alanine aminotransferase and lactate dehydrogenase levels, tissue xanthine oxidoreductase (XOR) and myeloperoxidase (MPO) activities, and expressions of NOX2 and NOX4 proteins were determined.

Results

Liver IR resulted in significant increases in NOX2 and NOX4 expressions and XOR and MPO activities, and approximately 2-fold increases in the levels of the inflammatory cytokines TNF-α and HMGB1. The microvascular blood flow and tissue oxygen saturation decreased by ∼20% from control values. GPC administration ameliorated the postischemic microcirculatory deterioration and reduced the liver necroenzyme levels significantly; the NOX4 expression, MPO activity, and HMGB1 level were also decreased, whereas the NOX2 expression, TNF-α level, and XOR activity were not influenced by GPC pretreatment.

Conclusions

NOX4 activation is a decisive component in the IR-induced microcirculatory dysfunction. Exogenous GPC ameliorates the inflammatory activation, and preserves the postischemic microvascular perfusion and liver functions, these effects being associated with a reduced hepatic expression of NOX4.     

Lipoxin A4 Attenuates Acute Rejection Via Shifting Th1/Th2 Cytokine Balance in Rat Liver Transplantation

Aims

To study the role of lipoxin A4 (LXA4) in rat liver transplant rejection.

Methods

An acute rejection model of liver transplantation was established in inbred rats DA to LEW that were randomly divided into a control group and a LXA4 group. Liver morphologic changes were examined using hematoxylin/eosin staining. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were quantified to measure liver injury. Intragraft mRNA and protein expressions of interferon (IFN)-γ interleukin and (IL)-10 were detected by real-time polymerase chain reaction and Western blots, respectively. The serum levels of IFN-γ and IL-10 were assayed by enzyme-linked immunosorbent assay.

Results

LXA4 treatment improved hepatic tissue injury as indicated by morphologic analysis. Serum ALT and AST levels were significantly decreased at day 7 post-transplantation (P < .05). Concurrently, expression of IFN-γ was downregulated (P < .05) and secretion of IL-10 was enhanced (P < .05).

Conclusions

LXA4 attenuated acute rejection with a parallel shift from Th1 to Th2 responses in rat liver transplantation.     

Effect of Ischemic Preconditioning and Postconditioning on Liver Regeneration in Prepubertal Rats

Background

Liver regeneration has great importance for transplantation, especially in children; however, it has not been studied sufficiently in development animals. Ischemia-reperfusion injury is a problem, and strategies such as ischemic preconditioning and postconditioning are not well defined regarding regeneration.

Objective

This study sought to evaluate liver regeneration with modulation by ischemic preconditioning and postconditioning in prepubertal rats subjected to total ischemia and reperfusion.

Methods

Thirty-five 5-week-old female Wistar rats were divided into groups of 7 animals each: control group (SHAM), 70% hepatectomy (HEP), total ischemia 30 minutes before hepatectomy (IR), ischemic preconditioning 10/10 minutes before ischemia (PRE), and two 30/30-second ischemic postconditioning cycles after ischemia and hepatectomy (POS). All animals were subjected to 24-hour reperfusion. Aspartate aminotransferase and alanine aminotransferase activity were measured to evaluate liver damage, and histological analysis, proliferating cell nuclear antigen (PCNA) and regenerated mass liver were used to evaluate liver regeneration. Statistical analyses were performed using ANOVA and Kruskal-Wallis test.

Results

Alanine aminotransferase and aspartate aminotransferase levels were significantly lower in conditioned groups than in the IR group. Regarding mitotic index, IR > control group and HEP (P < .05), PRE and POS were not significantly different from IR, and POS > HEP (P < .05). PCNA analysis showed that IR > HEP (P < .01), PRE < IR (P < .01), and no significant differences were observed between POS and IR groups. No significant differences in regenerated mass liver were observed between conditioned groups and HEP.

Conclusions

Ischemic postconditioning prevented ischemic injury, promoted greater liver regeneration, and should be further investigated as an alternative better than ischemic preconditioning.     

Remain recipient partial liver during liver transplant after Hassab

Background

The Hassab procedure is the primary method for treating and preventing recurrent esophagogastric variceal bleeding in portal hypertension patients. These patients have worsening liver function and eventually require liver transplantation. Abnormal anatomical structures and severe tissue adhesion caused by the Hassab procedure increase the risks of transplantation. We investigated the safety and efficacy of retaining part of the left lateral hepatic lobe during transplantation.

Materials and methods

This retrospective study evaluated outcomes in 22 patients who underwent the Hassab procedure followed by liver transplantation. The patients were separated into two groups: group A (complete liver resection, n = 14) and group B (incomplete liver resection with left lateral remnant, n = 8). We statistically analyzed pre-, intra-, and post-operative variables in both groups.

Results

Preoperative demographic data showed no significant differences between the groups. Operation time was significantly greater in group A (10.85 ± 0.79 h) than in group B (7.25 ± 0.59 h), and median blood loss (2807 ± 472 mL) was significantly greater in group A than in group B (1023 ± 141 mL, P < 0.05 for both). Overall complication rates were not significantly different; the 1- and 3-y survival rates were 85.7% and 71.4% for group A and 87.5% and 75.0% for group B, respectively (P > 0.05).

Conclusions

Retention of some left hepatic lobe tissue during liver transplantation after the Hassab procedure is safe and feasible because it increases the success rate by reducing surgical difficulty and time.     

Comparison Between Resection and Transplantation in Combined Hepatocellular and Cholangiocarcinoma

Objective

The treatment of choice for combined hepatocellular and cholangiocarcinoma (cHCC-CC) is surgical resection. However, the efficacy of liver transplantation is not clear. We compared the surgical outcome of hepatic resection and liver transplantation for cHCC-CC.

Patients and methods

From 1995 to 2012, 89 patients were diagnosed with cHCC-CC after hepatic resection and 8 patients diagnosed with cHCC-CC after liver transplantation. We excluded 21 patients who were American Joint Committee on Cancer Staging Stage III or IV and lost to follow-up. The outcomes were reviewed retrospectively.

Results

The poor prognostic factors in cHCC-CC patients who underwent hepatectomy were large tumor size (>5 cm), small safety margin (<2 cm), and low preoperative albumin level. The disease-free survival (DFS) and overall survival (OS) between the hepatectomy group (n = 68) and the liver transplant group (n = 8) was not statistically different (5-year DFS: 26.2% vs 37.5%, P = .333; 5-year OS: 42.1% vs 50%, P = .591). In the small tumor subgroup (tumor size <5 cm), the DFS and OS between the 2 surgical procedures was not different, and in the adequate resection margin subgroup (safety margin >2 cm), survival was comparable.

Conclusions

In well-selected cases with small tumor size and with preserved liver function, liver resection should be considered when complete resection is possible.     

Superparamagnetic iron oxide magnetic nanomaterial-labeled bone marrow mesenchymal stem cells for rat liver repair after hepatectomy

Background

Superparamagnetic iron oxide magnetic nanomaterials (SPIO) are tracers used for treatment of central nervous and cardiovascular system complications in animal models. The present study investigated survival and proliferation of SPIO-labeled bone marrow mesenchymal stem cells (BMSCs) to determine their potential therapeutic value in liver repair.

Methods

Surface antigens of BMSCs were measured using flow cytometry. BMSCs viability, growth curve, and SPIO (0–100 μg/mL) labeling rate were evaluated using trypan blue staining, 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), and Prussian blue staining, respectively. SPIO-labeled BMSCs were transplanted via liver or spleen injection in rats undergoing 70% hepatectomy. Distribution of SPIO-labeled BMSCs in liver and spleen, and liver repair were evaluated by magnetic resonance imaging (MRI), and serum alanine aminotransferase, aspartate aminotransferase, albumin, and total bilirubin levels.

Results

CD29⁺/CD90⁺/CD45⁻ BMSCs were successfully isolated from rats. Labeling rate of SPIO in 25 μg/mLwas 94.9%. SPIO labeling did not affect BMSCs survival and proliferation. MRI showed that BMSCs colonized in the liver, whether via spleen or liver injection. Serum levels of alanine aminotransferase, aspartate aminotransferase, and total bilirubin in the transplanted rats were significantly lower than in the hepatectomy group at days 1, 3, and 7 after hepatectomy (all P < 0.05), whereas serum albumin levels were significantly higher in the transplanted rats on posthepatectomy day 3 (both P < 0.05). These indicators were not significantly different between the spleen and liver injection approaches.

Conclusions

BMSCs transplantation via liver or spleen injection could significantly accelerate liver healing. In vivo MRI of SPIO-labeled BMSCs can be used to trace real-time liver healing during clinical treatment after hepatectomy.     

A novel in situ model of liver cold ischemia–reperfusion in rats

Background

Orthotopic liver transplantation (OLT) is being used for studying cold ischemia reperfusion (I/R)-induced injury in experimental animals, but the technique is complicated and it does not accurately reflect the pathophysiology. Here, we report a novel model, termed “in situ liver cold ischemia (ISLCI)”, in Wistar rats.

Methods

ISLCI was achieved in rats by establishing a portal-jugular shunt and a cannula shunt in inferior vena cava, and the liver was continuously perfused with lactate Ringer's solution at a speed of 150 mL/h through the portal vein for 60 min. Portal venous pressure, serum levels of total bilirubin, alkaline phosphatase, alanine aminotransferase and γ-glutamyl transpeptidase (GGT), and hepatic histopathology were examined, and compared with rats undergoing OLT, in which the donor liver was subjected to a 60 min cold ischemia.

Results

Livers from ISLCI and OLT rats showed histopathologic changes characteristic of I/R-induced injury when examined on days 1 and 7, with complete recovery 14 d after reperfusion. Compared with OLT rats, ISLCI rats had significantly lower levels of portal venous pressure 1 and 10 min after porta hepatis clamping. They suffered a milder degree of I/R-induced hepatic injury, reflected by significantly lower levels of GGT, alanine aminotransferase, and alkaline phosphatase on day 1, and a significant lower level of GGT and a lower histopathologic score on day 7 after reperfusion.

Conclusions

Our preliminary results indicate that the ISLCI model is reliable and technically easier, and is superior to OLT for studying cold I/R injury.     

Effects of Organic Apricot on Liver Regeneration After Partial Hepatectomy in Rats

Background

The present study investigated the effects of (sun-dried organic apricot/SDOA) supplementation in chow on liver regeneration after partial hepatectomy/(PH) in rats.

Method

In this study, 28 female rats were randomized into four groups. On the 7th day of the study, group 1 underwent laparoscopic intervention while a PH was performed on the other three cohorts. On day 28, all rats were humanely killed. Blood and liver tissue samples were subjected to biochemical determinations, histological examinations, and measurement of tissue oxidative stress enzyme activity.

Results

Serum levels of alanine transaminase (ALT), alkaline phosphatase (ALP), and liver tissue glutathione (GSH) activities were affected by PH and/or SDOA consumption (P < .05). Moderately staining cell counts in group 4 were significantly different from the other three groups (P < .05). However, no significant differences were detected among all groups in regard to aspartate aminotransferase (AST) serum levels or liver tissue superoxide dismutase (SOD), malondialdehyde (MDA), catalase (CAT) or glutathione peroxidase (GSHpx) activities (P < .05).

Conclusion

The 5% SDOA supplementation over a 21-day feeding period showed a beneficial effect on liver regeneration in rats, as reflects by Ki-67 finding although there was no change in ALT or ALP or in liver tissue GSH activity.     

Impact of oxygen free radicals in rat partial liver transplantation

Background

Due to the shortage of suitable organs, the demand for partial liver transplantation from living donors has increased worldwide. N-acetylcysteine (NAC) has shown protective effects as a free radical scavenger during hypothermic preservation and warm ischemia–reperfusion liver injury; however, no study has reported the effects in partial liver transplantation. The aim of this study was to analyze the impact of NAC on liver graft microcirculation and graft function after partial liver transplantation in rats.

Methods

Orthotopic partial liver transplantations were performed in 40 rats following cold storage in histidine-tryptophan-ketoglutarate solution for 3 h with 20 mM NAC (NAC group, n = 20) or without (control group, n = 20). We assessed portal circulation, graft microcirculation, and biochemical analyses of plasma at 1, 3, 24, and 168 h after portal reperfusion.

Results

(Control versus NAC, median and range): Portal venous pressure was significantly lower with NAC (P = 0.03). Microcirculation measured by laser Doppler was significantly improved with NAC throughout the time course (P = 0.003). Alanine aminotransferase levels were significantly lower in the NAC group (P < 0.05). Total antioxidative capacity was significantly higher in the NAC group at 1 h after reperfusion (Trolox equivalents: median, 3 μM; range, 2.9–6.7 versus median, 16.45 μM; range, 10.4–18.8). Lipid peroxidation was significantly abrogated in the NAC group (median, 177.6 nmol/mL; range, 75.9–398.1 versus median, 71.5 nmol/mL; range, 58.5–79 at 3 h).

Conclusions

This study showed that NAC treatment during cold storage resulted in improved microcirculation and preservation quality of partial liver graft likely because of enhanced antioxidant capacity and reduced lipid peroxidation.     

Mast cell degranulation promotes ischemia–reperfusion injury in rat liver

Background

Mast cells (MCs) play a role in ischemia–reperfusion (I/R) injury in many organs. However, a recent study found that MCs are not involved in I/R injury in isolated rat livers that were perfused only for 1 h. The purpose of this study is to reevaluate the role of MCs in hepatic I/R injury in rat.

Materials and methods

A warm hepatic I/R injury model of 1 h ischemia followed by 24 h of reperfusion was used. MC modulation was induced via cromolyn injection or a method called MC depletion using compound 48/80. The effects of MC modulation were evaluated by toluidine blue staining and assessment of mast cell tryptase in sera. The role of MCs in I/R injury was evaluated by hematoxylin and eosin staining graded by Suzuki criteria, alanine aminotransferase and aspartate aminotransferase levels in sera, and malondialdehyde levels in liver homogenates.

Results

First, MC degranulation peaked after 2 h of reperfusion and liver damage peaked after approximately 6 h of reperfusion. Second, a method called MC depletion previously used in the skin with repeated injections of compound 48/80 worked similarly in the hepatic setting. Third, stabilization of MCs with cromolyn or depletion of MCs with compound 48/80 each decreased hepatic I/R injury. The most noticeable effects of cromolyn and compound 48/80 treatment were observed after approximately 6 h of reperfusion.

Conclusions

MC degranulation promotes hepatic I/R injury in rats.     

Clinical Outcome of Internal Stent for Biliary Anastomosis in Liver Transplantation

Background

This study analyzed the incidence and management of biliary complications after liver transplantation (LT) with or without internal stent.

Methods

The medical record of all patients who underwent LT and were hospitalized from December 2009 to March 2013 were reviewed. Patients were grouped into 2 groups (internal stent group vs no stent group).

Results

There were 29 deceased-donor liver transplantations (58%) and 21 living-donor liver transplantations (42%). There were 2 perioperative mortalities, and those 2 patients were excluded from this study. The overall biliary complication rate was 6.45% in the internal stent group and 17.65% in the no stent group. The rate of anastomotic stricture was 3.23% (n = 1) in the stent group and 11.76% (n = 2) in the no stent group. The rate of bile leak was 3.23% (n = 1) in the stent group and 0% in the no stent group. The rate of biliary obstruction was 0% in the stent group and 5.88% (n = 1) in the no stent group.

Conclusions

The overall rate of biliary complications in the internal stent group was lower than in the no stent group, and most of the biliary complications could be treated successfully with endoscopic or radiologic intervention.     

A novel model for orthotopic liver transplantation in rats using hepatic rearterialization and biliary extradrainage system

Background

Although the rat orthotopic liver transplantation (OLT) model has existed for many years, only a few models can be applied for dynamic bile collection. The aim of this study was to introduce a dependent rat OLT model with hepatic rearterialization and an expediently dynamic bile collection system.

Methods

Forty-five male Sprague–Dawley rats were divided into the following three groups (n = 15 each): group A, OLT without hepatic rearterialization; group B, OLT with hepatic rearterialization; group C, OLT with hepatic rearterialization and a biliary extradrainage system. In groups B and C, a modified sleeve anastomosis between the donor common hepatic artery and the recipient proper hepatic artery was performed to restore the hepatic artery blood flow. In group C, after hepatic rearterialization, biliary extradrainage and jejunum stoma were performed to reestablish the bile flow, and a waistcoat-like external fixator was introduced to protect this system.

Results

The surgical success rates in groups A, B, and C were 100% (15/15), 93% (14/15), and 93% (14/15), respectively. In groups B and C, the hepatic artery patency rates were 93% and 86% on postoperative day 3 and postoperative day 21, respectively. Also, the liver function and bile duct integrity were preserved better than that in group A. In group C, the biliary extradrainage system was well preserved and bile collection was easily performed.

Conclusions

The rat OLT model with hepatic rearterialization and a convenient biliary extradrainage system was satisfactory in maintaining the survival rate, hepatic artery patency rate, and recovery of graft function, so it can be applied in various studies after transplantation.     

Should Preconditioning Hyperbaric Oxygenation Protect the Liver Against Ischemia–Reperfusion Injury? An Experimental Study in a Rat Model

Objectives

We designed studies to test the hypotheses that hyperbaric oxygen (HBO) therapy should protect liver against subsequent ischemia/reperfusion (I/R) injury are scarce and controversial. The purpose of this study was to clarify some questions about the association of HBO with the processes of liver I/R.

Methods

We divided Wistar rats into 5 groups: (1) SHAM operation, (2) I/R, rats submitted to total pedicle ischemia for 30 minutes followed by 5 minutes of reperfusion; (3) HBO60I/R and (4) HBO120I/R, rats respectively submitted to 60 and 120 minutes of HBO therapy at 2 absolute atmospheres and immediately after submitted to the experimental protocol of I/R; (5) HBO120, rats submitted to 120 minutes of HBO therapy at 2 absolute atmospheres and then immediately after humanely killed. The experimental protocol included (1) serum levels of aspartate and alanine aminotransferase; (2) mitochondrial function; (3) tissue malondialdehyde (MDA); and (4) plasma nitrite/nitrate. Data were analyzed using the Mann–Whitney test and were considered significant P < 5%.

Results

The processes of liver ischemia/reperfusion caused tissue injury with hepatic mitochondrial functional impairment. A single exposure to 120 minutes of HBO caused an increase of tissue MDA. The time of HBO exposure as preconditioning before hepatic I/R is critical in the prevalence of beneficial or deleterious effects. Sixty minutes of hyperoxic preconditioning before liver I/R presents systemic benefits, but no significant tissue preservation. One hundred twenty minutes of hyperoxic preconditioning tissue liver benefits predominate compared with systemic benefits.

Conclusions

The HBO preconditioning therapeutic benefits to liver I/R injury are time dependent, suggesting a therapeutic window that needs to be clearly defined in future studies.     

Does Procurement Technique Affect Posttransplant Graft Function in Deceased Donor Liver Transplantation?

Introduction

Various techniques have been described deceased donor liver transplantation (DDLT) procurement. One is a technique whereby almost total dissection is done in the porta hepatis and perihepatic detachment is carried out before cross-clamping the donor aorta. In another approach, after the donor aorta is cross-clamped, rapid and minimal en bloc dissection is performed with minimal manipulation. We evaluated early posttransplant graft function among liver procurement techniques.

Method

Between January 2008 and August 2012, we performed 45 consecutive adult DDLTs. One patient was excluded from this analysis due to early death from sepsis after transplantation. The 44 included patients were divided into two cohorts according to the procurement technique: A warm dissection (n = 23; 52%) and a cold dissection group (n = 21; 48%). We compared early posttransplant graft function using the aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (T-bil), and prothrombin time (PT) values of the two groups from the first to seventh postoperative day.

Result

The AST values in the warm group were significantly greater than those in the cold group on postoperative days 3 and 5. In addition, the ALT values in the warm group were greater than those in the cold group on postoperative days 4, 5, and 6. Moreover, the T-bil values in the warm group were greater than those in the cold group on postoperative days 2, 3, 4, 5, 6, and 7. However, there were no differences in PT values.

Conclusion

During liver procurement for DDLT, rapid en bloc procurement with minimal manipulation after clamping the donor aorta achieved better early graft function posttransplantation.     

Postoperative but not preoperative treatment with sorafenib inhibits liver regeneration in rats

Background

Sorafenib, a multikinase inhibitor, has been shown to halt the growth of hepatocellular carcinoma. The aim of the present study was to investigate the effect of Sorafenib on liver regeneration in healthy rats.

Methods

In two substudies we examined the effect of pre- or post-operative treatment with Sorafenib (15 mg/kg/d). Wistar rats (n = 120) received either Sorafenib (S) or placebo (P). After 70% partial hepatectomy, the rats were euthanized on postoperative days 2, 4, or 8. Body weight and liver weight were recorded and regeneration rate (RR) calculated. Hepatocyte proliferation was estimated by immunohistochemistry for Ki-67 antigen using unbiased stereological methods.

Results

Eleven animals (9%) died after surgery. In the preoperative substudy, lower body weight gains during the gavage period in the S group were found. No difference between groups S and P regarding liver weight gain, liver RRs, and hepatocyte proliferation on postoperative days 2 and 4 were found. In the postoperative substudy, significantly lower values of liver weight gain, liver RRs, and hepatocyte proliferation were found in the S group.

Conclusions

In our rat model, Sorafenib did not increase posthepatectomy mortality. Postoperative treatment significantly impaired liver regeneration. Preoperative treatment impaired body weight during the gavage period, but was without effect on liver regeneration.     

Impact of the hepatic branch of the vagus and Roux-en-Y gastric bypass on the hypoglycemic effect and glucagon-like peptide-1 in rats with type 2 diabetes mellitus

Background

The impact of the hepatic branch of the vagus and Roux-en-Y gastric bypass (RYGB) on the hypoglycemic effect and glucagon-like peptide-1 (GLP-1) in rats with type 2 diabetes mellitus (T2DM) was investigated, and interactions were preliminarily analyzed.

Methods

A total of 45 rats with T2DM were divided into four groups: sham operation (S, n = 10), sham operation with the hepatic branch of the vagus resected (SV, n = 11), RYGB (n = 12), and RYGB without preservation of the vagus (RYGBV, n = 12). Body mass, fasting blood glucose (FBG), fasting serum insulin, and concentrations of fasting serum GLP-1 were examined in the first, second, fourth, and eighth week before and after surgery. The effects of RYGB and the hepatic branch of the vagus on GLP-1 levels in the eighth postoperative week were also analyzed.

Results

RYGB caused a significant reduction in the weight of rats with T2DM (P < 0.05), improved the levels of serum GLP-1 and insulin (P < 0.05), and decreased FBG level (P < 0.05). Retention of the hepatic branch of the vagus maintained weight reduction for a longer period (P < 0.05) and increased the levels of serum GLP-1 and insulin (P < 0.05), but had no impact on FBG level (P > 0.05).

Conclusions

RYGB had better therapeutic efficacy in rats with T2DM. Care should be taken during RYGB surgery to preserve the hepatic branch of the vagus.     

Augmenter of liver regeneration attenuates inflammatory response in the postischemic mouse liver in vivo

Background

Augmenter of Liver Regeneration (ALR), a protein synthesized in the liver is suggested to be protective against oxidative stress–induced cell death. Hepatic ischemia–reperfusion (I/R) injury is triggered by reactive oxygen species. Here, we tested the hypothesis that ALR attenuates hepatic I/R injury in vivo.

Methods

C57BL6 mice were subjected to warm hepatic ischemia for 90 min. Either recombinant ALR (100 μg/kg) or vehicle were administered to mice prior ischemia. During reperfusion, neutrophil and CD4+ T cell migration and sinusoidal perfusion were analyzed using intravital microscopy. Alanine aminotransferase–aspartate aminotransferase (plasma) and caspase-3 (tissue) activities were determined as markers of hepatocellular necrotic and apoptotic injury.

Results

Hepatic I/R led to dramatic enhancement of neutrophil and CD4+ T cell recruitment in hepatic microvessels, sinusoidal perfusion failure, and strong elevation of aspartate aminotransferase–alanine aminotransferase and caspase-3 activities. During early reperfusion (60 min), the pretreatment with ALR improved postischemic perfusion failure (P < 0.05) and attenuated liver enzyme activities. Recruitment of CD4+ T cells, but not of neutrophils was attenuated. After 240 min of reperfusion, the protective effect of ALR was stronger, since the liver enzyme activity, perfusion failure, and leukocyte influx were significantly attenuated. As shown by the measurement of caspase-3 activity, postischemic apoptosis was reduced in the ALR-treated group.

Conclusions

Our in vivo data show that ALR has a therapeutic potential against postischemic liver injury. As a mechanism, we suggest a direct protective effect of ALR on apoptotic and necrotic death of hepatocytes and an attenuation of inflammatory cell influx into the postischemic tissue.     

Liver Resection in Transplanted Patients: A Single-Center Western Experience

Background

Liver resection (LR) in liver transplant (OLT) recipients, an extremely rare situation, who performed on 8 recipients.

Methods

This retrospective analysis of prospectively collected data concerned 8 (0.66%) 1198 LR cases among OLT performed from 1997 to 2011. We analyzed demographic data, surgical indications, and postoperative courses.

Results

The indications were resectable recurrent hepatocellular carcinomas (HCC, n = 3), persistent fistula from a posterior sectorial duct (n = 1), recurrent cholangitis due to anastomotic stricture on the posterior sectorial duct (n = l), hydatid cyst (n = l), left arterial hepatic thrombosis with secondary ischemic cholangitis (n = 1), and a large symptomatic biliary cyst (n = 1). The mean interval time to liver resection was 23.7 months (range, 5–47). LR included right hepatectomy (n = 1), right posterior hepatectomy (n = 1), left lobectomy (n = 4), pericystectomy (n = 1), or biliary fenestration (n = 1). Which there was no postoperative mortality, the global morbidity rate was 62% (5/8). The mean follow-up after LR was 92 months (range, 11–156). No patients required retransplantation. None of the 3 patients who underwent LR for HCC showed a recurrence.

Conclusions

LR in OLT recipients is safe, but associated with a high morbidity rate. This procedure can avoid retransplantation in highly selected patients, presenting a possible option particularly for transplanted patients with a resectable, recurrent HCC.     

Difference in Outcomes Between Living Left Lobe Donors and Noncirrhotic Subjects Undergoing Left Lobe Resections

Objectives

The aim of this study was to compare short- and long-term outcomes between the living donors and patients without cirrhosis after left lobe resection.

Material and Methods

We retrospectively collected data from 40 left lobe donors (Group 1) and from 40 patients who had undergone left liver resection for various diseases (Group 2) from 2002 to 2010. In addition to preoperative parameters, we compared intraoperative variables as well as, short- and long-term outcomes, including postoperative complications and laboratory test results. The liver functions included total bilurubin (TB), aspartate aminotransferase (AST), alanine aminotransferase (ALT), international normalized ratio (INR), and albumin (ALB) compared as well as changes in white blood cell (WBC) count and platelet count.

Results

The preoperative parameters of the two groups were comparable. There was significantly more blood loss in Group 2 than Group 1 (422.5 mL vs 318.8 mL; P = .001), leading to more autologous blood transfusions in Group 2 (P = .008). The other intraoperative variables were similar between the two groups. The overall postoperative complication rate was similar: 4% in Group 1 and 8% in Group 2 (P = .213); however, there were longer hospital stays and overall costs in Group 1 (P < .05). The total bilirubin level, AST, and ALT of Group 2 were worse than those in Group 1 during the early postoperative period. Upon long-term follow-up the postoperative platelet count decreased in the two groups compared with the preoperative levels.

Conclusion

The type and rate of complications following left hepatectomy were similar between donors and noncirrhotic hepatic patients. Nevertheless, more serious liver dysfunction postoperatively was observed among the patient group.